Drug & supplement interaction

Red Clover + Naproxen

Naproxen brand names: Naprosyn, Naprelan, Anaprox, Anaprox DS, Naproxyn, and others.

Minor Interaction
The bottom line Minor

Naproxen falls into 3 drug categories that Red Clover can interact with; the most serious is rated minor. Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.

Read the full interaction report
SeverityMinor
LikelihoodUnlikely
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Red Clover and Naproxen

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Red Clover interacts with whole categories of medication. Naproxen falls into 3 of those categories, so it can interact with Red Clover in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Minor).

Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 3

Why this applies to Naproxen

Naproxen falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Red Clover interacts with.

Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
In vitro evidence shows that red clover inhibits CYP1A2. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version: this one is mostly theoretical, so I wouldn't lose sleep over it. In lab dish (test tube) studies, red clover slowed down an enzyme called CYP1A2, which is one of the pathways your body uses to clear naproxen. If that slowdown happened in real life, naproxen could build up a bit and you might notice more of its usual effects, like stomach upset, heartburn, or in rare cases stomach irritation.

But here's the reassuring part: an actual human study using a standardized red clover dose found no real change in how the body handled a similar test drug. So the risk here looks low. Naproxen is not a prodrug, so it doesn't get flipped around. Still, if you take naproxen regularly, it's worth a quick chat with your pharmacist before adding red clover.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

2 of 3

Naproxen also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.

Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.
In vitro evidence suggests that red clover might inhibit CYP2C9. However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate.
Severity Minor Likelihood Unlikely Evidence D

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for naproxen: your liver uses an enzyme called CYP2C9 to help clear it out. In a test tube, red clover looked like it might slow that enzyme down, which could theoretically let naproxen build up a little and nudge up the usual side effects, things like stomach upset, heartburn, or a higher chance of stomach irritation.

The reassuring part is that this is mostly lab-dish data. When researchers actually gave people red clover capsules (standardized to 60 mg isoflavones twice daily) for two weeks, it did not change how a similar CYP2C9 drug behaved. So a real-world problem is unlikely. Naproxen is not a prodrug, so it doesn't flip. Still, if you take both regularly, mention it to your pharmacist or doctor.

References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  2. Chen L, Choi J, Leonard SW, et al. No Clinically Relevant Pharmacokinetic Interactions of a Red Clover Dietary Supplement with Cytochrome P450 Enzymes in Women. J Agric Food Chem. 2020;68(47):13929-13939. PubMed
Minor

ANTICOAGULANT/ANTIPLATELET DRUGS

3 of 3

Naproxen also falls under ANTICOAGULANT/ANTIPLATELET DRUGS.

Although some laboratory research suggests that red clover may have anticoagulant and antiplatelet activity, clinical research has not shown this effect.
In vitro research suggests that genistein in red clover has antiplatelet effects, and historically, red clover was thought to have anticoagulant effects due to its coumarin content. However, some experts state that this is unlikely as most natural coumarins have not been shown to have anticoagulant effects, and their content in red clover is low. Additionally, some clinical research in postmenopausal patients found no effect on coagulation or prothrombin time with the use of red clover flowering tops 378 mg daily for 12 months or red clover isoflavone (Rimostil) 50 mg daily for 2 years.
Severity Minor Likelihood Unlikely Evidence B

Interaction has been demonstrated in animal or in lab research but has been shown not to occur in humans..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist for naproxen and red clover. The worry is that both might thin the blood a little. Naproxen, an NSAID, can already irritate the stomach and make bleeding or bruising more likely. The thinking was that red clover's plant compounds (like genistein) plus its small amount of coumarins could add to that. So in theory, the combo might nudge your bleeding risk up a bit.

But here's the reassuring part: real human studies don't back this up. Postmenopausal women who took red clover daily for one to two years showed no change in clotting tests. So this is a minor and unlikely concern. Still, if you notice easy bruising, dark stools, or stomach upset, or you take other blood thinners, give your pharmacist or doctor a quick call.

References
  1. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause 2009;16:1156-66. PubMed
  2. Guerrero JA, Lozano ML, Castillo J, et al. Flavonoids inhibit platelet function through binding to the thromboxane A2 receptor. J Thromb Haemost 2005;3(2):369-376. PubMed
  3. Kondo K, Suzuki Y, Ikeda Y, Umemura K. Genistein, an isoflavone included in soy, inhibits thrombotic vessel occlusion in the mouse femoral artery and in vitro platelet aggregation. Eur J Pharmacol 2002;455(1):53-57. PubMed
  4. Polini N, Rauschemberger MB, Mendiberri J, et al. Effect of genistein and raloxifene on vascular dependent platelet aggregation. Mol Cell Endocrinol 2007;267(1-2):55-62. PubMed
  5. Clifton-Bligh PB, et al. Red cover isoflavones enriched with formononetin lower serum LDL cholesterol- a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr. 2015;69(1):134-142.

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Red Clover Also Interacts With Other Medications

Red Clover has 44 moderate, 822 minor known drug interactions in our database — the Naproxen one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Red Clover

Covers the 2,830 medications we’ve checked against Red Clover. Pick one to open its full report.

From our Q&A

Questions About Red Clover or Naproxen

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Red Clover or Naproxen, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Naproxen

This page covers Red Clover only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Naproxen page lists 311 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Danshen (major) and Piracetam (major).

By severity: 7 major · 260 moderate · 44 minor.

Open the Naproxen interaction page

One more smart check

Taking Red Clover as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,480 real supplement products containing Red Clover, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Red Clover. Your product may carry other ingredients that interact with Naproxen too, on top of Red Clover — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Red Clover and Naproxen Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Red Clover
Top 25%

#162 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Naproxen
Top 5%

#52 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Red Clover

What is Red Clover?

Red Clover
  • Menopause symptoms (hot flashes)
  • High cholesterol
  • Bone health/osteoporosis
  • Skin and hair concerns
  • Women's health

Red clover is a plant rich in isoflavones (plant compounds with weak estrogen-like activity) that is most often used for menopause symptoms like hot flashes. The evidence is mixed and generally weak, with some studies showing modest benefit and others showing none. Because of its hormone-like effects, it's not for everyone—talk with your pharmacist or doctor before trying it, especially if you have a hormone-sensitive condition.

Read the full Red Clover monograph & all interactions
Medication

About Naproxen

What Is Naproxen Used For?

Brand names: Naprosyn, Naprelan, Anaprox, Anaprox DS, Naproxyn, Navalbine, Naproxen, Naprosyn EC, Napro-Na, Aleve, Arthroxen, Synflex, EC-Naprosyn

Naproxen tablets, naproxen sodium tablets, and naproxen oral suspension are used to relieve the signs and symptoms of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis. They are also used for tendonitis, bursitis, and acute gout, and for managing pain and primary dysmenorrhea (menstrual cramps).

Naproxen Sodium Controlled-Release Tablets are indicated for the same conditions plus the relief of mild to moderate pain. Several over-the-counter naproxen sodium products are indicated for the temporary relief of minor aches and pains from headache, backache, muscular aches, toothache, menstrual cramps, minor arthritis pain, and the common cold, and to temporarily reduce fever.

See full Naproxen drug information
Keep checking

Other Drugs & Red Clover

Browse every other medication we’ve checked against Red Clover — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
44Moderate
822Minor
1,963No known interaction
Moderate

44 interactions

Minor

822 interactions

Showing 60 of 822 minor interactions — see all 822 on the Red Clover page.

No interaction 1,963 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Red Clover and Naproxen Together: Common Questions

Can you take Red Clover with Naproxen?
There is only a minor interaction, which is usually not serious. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Red Clover and Naproxen?
Naproxen belongs to more than one drug category, and Red Clover interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Red Clover and Naproxen interaction?
We rate it Minor. This interaction is generally not clinically significant, but it remains worth noting and discussing with your pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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